Microlead for multipoint neuromodulation of the central nervous system

ABSTRACT

A microlead, of an overall diameter less than 0.5 mm, includes a plurality of at least eight conductor wires individually insulated and twisted together. Each conductor wire includes an electrically conductive core microcable and an insulation layer surrounding the core microcable and having at least one exposed area to form a detection/stimulation electrode of the microlead. The microlead further includes a central support structure shaped as a surface of revolution, which may be free of conductor wires and of central lumen. The conductor wires are configured in one or more layers of twisted peripheral conductor wires carried by the central support structure and circumferentially distributed thereon.

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/044,927, filed Feb. 16, 2016, which claims the benefit of andpriority to French Patent Application No. 1551295, filed Feb. 17, 2015,both of which are incorporated herein by reference in their entirety.

BACKGROUND

The invention relates to “active implantable medical devices” as definedby Directive 90/385/EEC of 20 Jun. 1990 of the Council of the EuropeanCommunities.

It is more specifically related to a neuromodulation microlead operatingby multipoint stimulation of the central nervous system.

A neuromodulation lead is typically designed to be implanted in thecerebral venous network in order to target specific areas of the brainto apply electrical neurostimulation pulses for treating certainpathologies such as Parkinson's disease, epilepsy, etc. These techniquesare grouped under the general term deep brain stimulation (DBS). Thepurpose of the lead may also be to stimulate the spinal cord, inparticular for the treatment of pain. These techniques are known underthe general name spinal cord stimulation (SCS).

These techniques differ in many aspects, including the methods used,from those employed in cardiology or in other types of nerve stimulationwhere the peripheral nervous system is stimulated, as in techniquesknown as vagus nerve stimulation (VNS) or analog techniques, where theelectrodes are placed next to nerves or muscles, consequently in muchmore easily accessible areas.

The specificity of the leads for the stimulation of the central nervoussystem may results in the diameter of these leads being less than 1.5French, or 0.5 mm, as well as having a lower number of electrodes toallow “multipoint” stimulation.

According to exemplary embodiments, the present disclosure provides amicrolead structure that is able to reach deep brain areas in regionsknown as potentially effective in neuromodulation therapy, known underthe name of the subthalamic nucleus (STN) or internal globus pallidus(GPI), and to precisely stimulate target areas located in these regions.

Current solutions of deep neurostimulation generally use a highlyinvasive approach, based on the perforation of the skull and on theimplantation of the lead with an external guiding.

However, it would be desirable to provide methods enabling a far lessinvasive approach, through a venous access, implementing techniquessimilar to those used for the microcatheterization of the brain, used inthe context of interventional neuroradiology. Provided that the leadshave a sufficiently small diameter structure and are able to navigate inthe venous and arterial system of the brain, these techniques could beused for the implantation of a microlead. In some implementations, themicrolead must, however, remain suitable for permanent implantation inthe brain.

Known microleads, however, face several major challenges using thesemethods.

First, leads of a too large diameter can cause severe neurologicaldamage during the surgical implantation procedure. It is thereforenecessary to greatly reduce the diameter of the microlead, while keepingits excellent maneuverability properties within the venous system toenable its implantation.

The cerebral arterial venous network includes high tortuosity and manybranches, and it is essential to avoid trauma that a too rigid leadcould provoke. But, conversely, too soft a microlead would be difficultto implant, due to a too low torsional stiffness to allow transmissionof a rotation movement given from the proximal end over the entirelength of the lead body until the distal end, (lack of “torquability”).Furthermore, a microlead that is too soft could not progress in thebiological network without jamming under the effect of an axial thrust(lack of “pushability”).

Second, it is desirable that the implantable lead is compatible with thecatheters of 1.6 French (0.53 mm) such as those already used today ininterventional neuroradiology, for example for the delivery of devicessuch as springs (coils) during the treatment of intracranial aneurysms.This implies a lead having an overall diameter of less than 1.5 French(0.5 mm).

Third, the electrodes of a neurostimulation microlead should have anextremely small surface, so as to specifically stimulate targeted areaswithout the risk of producing serious psychiatric side effects, whichunfortunately occurs today in a significant percentage of interventions.

Finally, it is desirable to have a very high number of neurostimulationelectrodes on the same microlead, all being independently selectable, soas to refine the accuracy of the stimulated contact points. In someembodiments, the microlead may have at least 8 (e.g., from 20 to 100)independently programmable electrodes, with the possibility to selectelectrodes located in different angular directions on the samelongitudinal position of the lead. This multiplication of the number ofelectrodes, and consequently of the independent conductors, may beimplemented without detriment to the small diameter of the microlead,which reduces its traumaticity and offers access opportunities to deepbrain areas.

Various neuromodulation lead structures with multiple conductors havebeen proposed, for example in WO 2007/115198 A2, US 2006/0111768 A1 orUS 2010/0057176 A1, but for a relatively small number of conductors, andconsequently the number of programmable electrodes (on the order of tenat most).

US 2006/0089697 A1 discloses a lead including a plurality of independentstranded conductors, distributed around a hollow tube, the assemblybeing protected by an outer insulation jacket. The tube is traversedthrough by a central lumen for permitting insertion of a delivery styletwhich is inserted into this lumen during implantation. The overalldiameter of this structure (at least 0.8 mm) is, however, much too highto achieve the deepest target areas of the brain.

US2013/0018445 A1 discloses a neurostimulation lead having up to 49conductor strands spirally wound and individually insulated, but in anapplication for stimulation of a peripheral nerve located in a muscle orin adipose tissue, which is in an environment where the constraints of avery small diameter and of navigability are not met.

EP 2581107 A1 and EP 2719422 A1 (Sorin CRM) describe implantablemicroleads structures in venous, arterial or lymphatic networks. Thesemicroleads however are primarily designed for implantation into thecoronary venous network for stimulation of the myocardium leftventricle, therefore in cardiology applications. Their structure isspecifically designed to withstand very severe fatigue stresses relatedto the heartbeat, which cause material fatigue as a result of repeatedbending from hundreds of millions of cycles, which can cause the lead tobreak and limit the lifespan.

These issues are much less critical in the case of a DBS or SCSneuromodulation microlead, which is implanted in a more staticenvironment than the heart and is much less prone to fatigue stresses.Moreover, multiplying the number of independent electrodes (e.g., atleast 8, such as from 20 to 100) cannot be satisfied by the microleadsstructures described in these documents, which may include at most sevenindependent conductors within a diameter of 1.5 French (0.5 mm).

SUMMARY

Thus, according to various exemplary embodiments, the present disclosureaims at solving the problem by providing a specifically adaptedmultipoint stimulation microlead for the central nervous system, whichmay provide:

-   -   the possibility of increasing the number of conductors in a        twisted structure which is compact, resistant to mechanical        stress in bending and flexible, having up to 100 insulated wires        in a dimension less than 0.5 mm;    -   the possibility of achieving, in this structure, very small        electrodes, and oriented in a plurality of axial directions; and    -   a microlead that is suited for long term implantation in        permanent neurological stimulation applications after        implantation in the cerebral venous network.

According to some embodiments, the disclosure provides a multipolarmicrolead with an overall diameter less than 1.5 French (0.5 mm)including at least eight conductor wires individually insulated andtwisted together. Each conductor wire includes a microcable having anelectrically conductive core, connected in the proximal portion to apole of a generator of an active implantable medical device; and aninsulation layer surrounding the core cable and having at least anexposed zone formed in the thickness of the insulation layer in thedistal portion to form a detection/stimulation electrode of themicrolead.

In some embodiments, the microlead further includes a central supportstructure having a revolution surface shape, the central supportstructure being free of i) conductor wires and of ii) central lumen, andthe conductor wires are configured in a layer of a twisted coil ofperipheral conductor wires carried by the central support structure andcircumferentially distributed thereon.

According to various embodiments:

-   -   a portion of the peripheral conductor wires are configured in a        first layer directly carried by the central support structure        and another part of the peripheral conductor wires are        configured in a second layer carried by the first layer;    -   the central support structure includes a single homogeneous        cylindrical element with a solid or tubular section, or a        plurality of homogeneous cylindrical elements stranded together,        with a solid or tubular section;    -   the central support structure includes a coil of a circuit        protecting against excess current induced during MRI        examination;    -   the overall diameter of the central support structure is greater        than the diameter of an individual conductor wire;    -   against bending stresses, the central support structure has a        capacity for elastic deformation higher than that of all the        individual conductor wires;    -   the central support structure is a tapered structure with a        decreasing diameter from the proximal region to the distal        region including a structure including a conical transition        portion between a proximal cylindrical portion of greater        diameter than that of the nominal unit diameter of an individual        conductor wire, and a cylindrical distal portion of smaller        diameter than the proximal portion;    -   the plurality of conductor wires include from 10 to 50 conductor        wires by layer; and    -   the unit diameter of an individual conductor wire is between 15        and 25 μm.

BRIEF DESCRIPTION OF THE DRAWINGS

Further features, characteristics and advantages of the presentdisclosure will become apparent to a person of ordinary skill in the artfrom the following detailed description of preferred embodiments of thepresent invention, made with reference to the drawings annexed, in whichlike reference characters refer to like elements and in which:

FIG. 1 generally illustrates an exemplary implantation of a microlead inthe cerebral vasculature according to an embodiment of the disclosure.

FIGS. 2a and 2b show in cross section and in side view respectively, theoverall structure of the microlead according to an embodiment of thedisclosure.

FIGS. 3a to 3d illustrate various embodiments of the central supportstructure of the microlead according to an embodiment of the disclosure.

FIG. 4 illustrates a particular embodiment of a microlead, with acentral support structure having a conical portion.

FIG. 5 illustrates, in cross section, an embodiment of a microleadaccording to the disclosure with twenty-six electrodes.

FIGS. 6 and 7 show an embodiment of the microlead in side view and incross section, including two layers of superimposed peripheralconductors, respectively.

FIG. 8 is a flow chart describing the various steps of an implantationprocedure of a microlead according to an exemplary embodiment of thedisclosure.

DETAILED DESCRIPTION

Various exemplary embodiments of the disclosure will now be described.

In FIG. 1, a microlead 10 according to an exemplary embodiment, thedisclosure is generally illustrated, implanted in the cerebralvasculature to selectively stimulate deep brain areas by localizedapplication of electrical pulses. The electrodes of the microlead mayalso act as, where appropriate, detection electrodes to collectelectrical potentials produced locally.

Stimulation of target areas of the brain involves implementation ofneuromodulation techniques for treating pathologies such as Parkinson'sdisease, epilepsy and other neurological diseases.

Consequently, in some implementations, it is necessary to access deepbrain regions, which are difficult to reach today with the knowntechniques.

Stimulation microleads for this purpose should not only have greatsolidity, so as to ensure long term biostability (these microleads maybe intended to be permanently implanted), but also a very small size(e.g., with an overall diameter less than 1.5 French (0.5 mm)). Inparticular, these 1.5 French microleads would be advantageouslycompatible with 1.6 French (0.53 mm) catheters, which are already usedin interventional neuroradiology, for example, for the release ofdevices such as coils for the treatment of intracranial aneurysms.

In some embodiments, these microleads bear a high number of electrodes(e.g., from 20 to 100 electrodes), which may be independently selectableso as to very precisely choose the stimulation zones according to thedesired effect. It is also desirable to be able to select the axialdirection in which these electrodes act, so as to optimize the resultingeffect and to avoid undesirable side effects.

FIGS. 2a and 2b show the microlead structure proposed by the presentdisclosure in section view and in side view, respectively, according toan exemplary embodiment.

The microlead 10 includes a central support structure 12 with arevolution surface shape (i.e., a shape generated by revolving astraight line or a curve around an axis), covered on its periphery by aplurality of peripheral conductor wires 14 carried by the centralsupport structure 12 and circumferentially spread thereof.

Each of these peripheral conductor wires 14 includes an electricallyconducting core microcable 16 and an insulation layer 18 surrounding thecore microcable.

The core microcable can be made of a conductor metal such as aPlatinum-Iridium alloy, a MP35N steel, Nitinol, etc. Various coremicrocable structures appropriate for this application are in particulardisclosed in the EP2581107 A1 (Sorin CRM) cited above, which can bereferred to for further details. It is also possible to use materialssuch as carbon nanotubes for the core microcable 16, which are materialswith exceptional mechanical resistance and with very good electricalconductivity characteristics.

For the insulation layer 18, materials such as polyurethanes (PU),polyester (PET), polyamides (PA), polycarbonates (PC), polyimides,fluoropolymers, polyether ether ketone (PEEK), poly-p-xylylene(parylene), or polymethyl methacrylate (PMM). However, preference may begiven to high chemical inertia materials such as fluoropolymers, whichalso have a very good insulation, particularly PTFE(polytetrafluoroethylene), FEP (perfluorinated propylene), PFA(perfluoroalkoxy copolymer resin), THV (tetrafluoroethylene,hexafluoropropylene, vinylidene fluoride), PVDF (polyvinylidenefluoride), EFEP (ethylene fluorinated ethylene propylene), or ETFE(ethylene tetrafluoroethylene) may be used.

Each of the conductor wires is present in the distal region of the leadin at least one exposed area (as shown at 38 or 38′ in FIG. 6) formed inthe thickness of the insulation layer, forming a detection/stimulationelectrode of the microlead.

The architecture of the microlead according to an exemplary embodimentof the disclosure, with a twisted coil of isolated peripheral conductorwires 14 carried by a central support structure 12, reduces the size ofthe lead in very large proportions while providing a large number ofinsulated electrical lines, connected to independent and thereforeprogrammable electrodes according to multiple configurations of thegenerator to which the microleads are connected.

Preferably, to minimize its size, this structure does not include acentral lumen (a channel opening at both ends of the lead), so for theimplantation of the microlead, the guiding is done externally via adelivery catheter, and not by a guidewire inserted into a central lumen.

FIGS. 3a to 3d illustrate various embodiments of the central supportstructure 12:

-   -   FIG. 3a : a simple core, formed of a homogeneous single strand        nucleus;    -   FIG. 3b : a core of a multi-strand nucleus, with several strands        20 embedded in a coating 22;    -   FIG. 3c : a tubular core 24; and    -   FIG. 3d : a support structure incorporating in its core a coil        26 of a circuit protecting against excess current induced in MM        examination situation.

The materials of the central support structure 12 may be selected and/orcombined depending on the desired final properties for the microlead, soas to provide the microlead with multiple features such as:

-   -   radiopacity, by incorporation of a metal such as tantalum,        palladium, gold or a platinum-iridium alloy in the material of        the central support structure 12;    -   shape memory, by use of polymers with properties of flexibility        and high elastic performance such as PEEK, PA, PEBA, PU, PET or        PFE; and    -   flexibility, “pushability” and “torquability”. The central        support structure 12 may present, against bending stresses, a        capacity for elastic deformation which is greater than that of        the individual conductor wires 14, this ability to the bending        deformation being required to go in the deep brain network.

As shown in FIG. 4, to further improve the performances of the microleadduring implantation, in particular the ability to advance lengthwise andcrosswise without jamming, it is possible to provide a cylindricalproximal portion 28 of a nominal diameter, connected to a distal portion30 smaller in diameter via a conical transition portion 32. The proximalportion 28 of larger diameter provides the “pushability”, that is to saythe ability of advancing the microlead under the effect of axial stressapplied for example by an operating handle from the proximal end, whilethe much thinner distal portion 30 enables the microlead to easily reachdeep, narrow, vessels of the brain region.

FIG. 5 illustrates an embodiment of a microlead according to thedisclosure with twenty-six electrodes, thus including twenty-sixperipheral conductor wires 14 carried by a central support structure 12.

The highly compact structure allows the use of insulated wires which canhave a diameter as small as 15-25 μm. Therefore it is possible to placeup to fifty conductor wires, and thus have as much independentelectrodes in an overall diameter of 0.40 mm for a unit wire conductordiameter of 25 μm (the number of conductors wires geometricallyincreasing by reducing the size of the conductors).

FIGS. 6 and 7 illustrate a variant including two superimposed layers ofconductors on the central support structure, with a first layer ofperipheral conductor wires 14 directly carried by the central supportstructure 12, and a second layer of peripheral conductor wires 14′carried by the first conductor layer 14. It is possible to independentlyoperate all the structural layers and thus increase the possibilitieswith up to over a hundred conductors 14 or 14′ independently operableeven in a structure in which the overall diameter does not exceed 0.5mm. The two layers of respective conductor wires 14 and 14′ can beaxially displaced, with a proximal zone 34 where the second conductivelayer 14′ is visible, and a distal region 36 where the surface ofconductors 14 of the first layer is visible. The proximal region 34carries the electrodes 38′ connected to the conductors 14′, while thedistal region 36 carries the electrodes 38 connected to the conductors14.

FIG. 8 schematically shows the different phases of the implantationmethod of the lead as described above.

This method is similar to that of a conventional lead, apart from thefact that due to the lack of internal lumen, it is not possible to use aguidewire to introduce the lead for guiding it in the vessels of thecerebral network. It is then preferred to use a microcatheter instead,according to procedures known by practitioners.

The first step (block 40) consists of introducing an assembly of amicrocatheter and a guidewire into the venous system up to the targetarea.

When the target area has been reached (block 42), the guidewire iswithdrawn, leaving in place the microcatheter.

The microlead is then introduced into the microcatheter (block 44), thenthe microcatheter is partially removed to gradually discover theelectrodes of the microlead (block 46).

Electrical tests are then automatically or manually carried out (block48). Once these tests are done, and it is confirmed that the lead isfully functional, the microcatheter is completely removed (block 50), orlocked in place if it is a microcatheter that can be permanentlyimplanted as described, for example, in EP 2 682 151 A1 (Sorin CRM).

The lead connector can then be connected to the pulse generator (block50) so that it can deliver neurostimulation pulses to the brain.

What is claimed is:
 1. A microlead for implantation in a cerebral venoussystem, comprising: a central support structure shaped in the form of asurface of revolution; and at least eight conductor wires individuallyinsulated and twisted together, each conductor wire comprising: anelectrically conductive core microcable comprising a proximal portionand a distal portion, the proximal portion structured to connect to apole of a generator of an active implantable medical device; aninsulation layer surrounding the core microcable; and an exposed areaformed in the insulation layer at the distal portion of the coremicrocable, the exposed area exposing a portion of the core microcableand forming an electrode of the microlead, the at least eight conductorwires arranged to form: a first layer of conductor wires twisted aroundthe central support structure; a second layer of conductor wires twistedaround the first layer of conductor wires on at least a proximal portionof the microlead; a proximal zone where the second layer of conductorwires are exposed to an exterior portion of the lead; and a distal zonewhere the first layer of conductor wires are exposed to the exteriorportion of the lead, wherein the lead has an outer diameter less than0.5 millimeters.
 2. The microlead of claim 1, wherein the lead islumenless.
 3. The microlead of claim 1, wherein the central supportstructure comprises a single homogeneous cylindrical element of solid ortubular section.
 4. The microlead of claim 1, wherein the centralsupport structure comprises a plurality of homogeneous cylindricalelements of solid or tubular sections stranded together.
 5. Themicrolead of claim 1, wherein the central support structure comprises acoil of a protection circuit protecting against over-current inducedduring an MRI.
 6. The microlead of claim 1, wherein an overall diameterof the central support structure is greater than a diameter of anindividual conductor wire.
 7. The microlead of claim 1, wherein, inresponse to bending stresses, the central support structure has acapacity for elastic deformation higher than that of all the conductorwires.
 8. The microlead of claim 1, wherein the at least eight conductorwires comprises 10 to 50 conductor wires in the first and second layersof conductor wires.
 9. The microlead of claim 1, wherein the individualdiameter of each conductor wire is between 15 and 25 μm.
 10. Themicrolead of claim 1, wherein the electrodes of the at least eightconductor wires are independently selectable.
 11. The microlead of claim1, wherein an axial direction that the electrodes of the at least eightconductor wires are acting can be selected.
 12. The microlead of claim1, wherein the microlead is structured to be implanted using amicrocatheter.
 13. An implantable medical device, comprising: agenerator structured to provide electrical stimulation; and a multipolarmicrolead for implantation in a cerebral venous system, comprising: acentral support structure shaped in the form of a surface of revolution;and at least eight conductor wires individually insulated and twistedtogether, each conductor wire comprising: an electrically conductivecore microcable comprising a proximal portion and a distal portion, theproximal portion structured to connect to a pole of a generator of anactive implantable medical device; an insulation layer surrounding thecore microcable; and an exposed area formed in the insulation layer atthe distal portion of the core microcable, the exposed area exposing aportion of the core microcable and forming an electrode of themicrolead, the at least eight conductor wires arranged to form: a firstlayer of conductor wires twisted around the central support structure; asecond layer of conductor wires twisted around the first layer ofconductor wires on at least a proximal portion of the microlead; aproximal zone where the second layer of conductor wires are exposed toan exterior portion of the lead; and a distal zone where the first layerof conductor wires are exposed to the exterior portion of the lead,wherein the lead has an outer diameter less than 0.5 millimeters. 14.The implantable medical device of claim 13, wherein the lead islumenless.
 15. The implantable medical device of claim 13, wherein thecentral support structure comprises a single homogenous cylindricalelement of solid or tubular section.
 16. The implantable medical deviceof claim 13, wherein the central support structure comprises a pluralityof homogeneous cylindrical elements of solid or tubular sectionsstranded together.
 17. The implantable medical device of claim 13,wherein the central support structure comprises a coil of a protectioncircuit protecting against over-current induced during an MRI.
 18. Theimplantable medical device of claim 13, wherein an overall diameter ofthe central support structure is greater than a diameter of anindividual conductor wire.
 19. The implantable medical device of claim13, wherein, in response to bending stresses, the central supportstructure has a capacity for elastic deformation higher than that of allthe conductor wires.
 20. The implantable medical device of claim 13,wherein the at least eight conductor wires comprises 10 to 50 conductorwires in the first and second layers of conductor wires.